Variant 12-80342167-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_001378609.3(OTOGL):c.5265+5G>A variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.00000259 in 1,545,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

OTOGL
NM_001378609.3 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.9957

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.80

Variant links:

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 12-80342167-G-A is Pathogenic according to our data. Variant chr12-80342167-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 39780.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-80342167-G-A is described in Lovd as [Likely_pathogenic]. Variant chr12-80342167-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.5265+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
OTOGL	ENST00000547103.7 linkuse as main transcript	c.5265+5G>A	splice_donor_5th_base_variant, intron_variant	5	NM_001378609.3	ENSP00000447211	P1
OTOGL	ENST00000298820.7 linkuse as main transcript	c.566+5G>A	splice_donor_5th_base_variant, intron_variant	5		ENSP00000298820
OTOGL	ENST00000646859.1 linkuse as main transcript	c.5130+5G>A	splice_donor_5th_base_variant, intron_variant			ENSP00000496036

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000582

AC:

AN:

171932

Hom.:

AF XY:

0.0000110

AC XY:

AN XY:

91290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1393796

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689960

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 84B

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 02, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.93

Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over